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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

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  1. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection DR. S.K CHATURVEDI DR. KANUPRIYA CHATURVEDI

  2. Antiretroviral (ARV) Therapy in Adults and Children • Similar pathogenesis of HIV infection • General virologic and immunologic principals for antiretroviral therapy apply • Unique considerations in infants, children, and adolescents

  3. Special Considerations in Pediatric ARV Therapy • Diagnostic issues • Pharmacokinetic changes • Availability of pediatric formulations • Natural history differences in virologic and immunologic markers • Adherence issues

  4. Changing Pharmacokinetics • Age-related differences between children & adults • Body composition • Renal excretion • Liver metabolism • Gastrointestinal function • Enzyme maturation • Drug distribution, metabolism and clearance • Drug dosing and toxicities Lead to potential differences in:

  5. Diagnostic Issues • Early identification = all pregnant women must be offered HIV counseling and testing • Perinatal infection = primary infection • Early diagnosis = starting therapy during primary/early infection

  6. Diagnostic Issues in Infants • HIV is diagnosed by 2 positive HIV virologic tests performed on blood samples 2 separate dates • Use DNA PCR or HIV culture for diagnosing at: • Birth (<48 hours) • 14 days (optimal) • 1–2 months • 3–6 months

  7. Diagnostic Issues in Infants • HIV is reasonably excluded with: • 2 or more negative virologic tests • One at age >1 month • One at age >4months • 2 or more negative HIV antibody tests at >6 months (in the absence of breast feeding)

  8. Pediatric HIV ClassificationAge-Specific CD4+ Immunologic Categories

  9. Pediatric HIV Classification Clinical Categories • Category E: Perinatally Exposed • Category N: Not Symptomatic • Category A: Mildly Symptomatic • Category B: Moderately Symptomatic • Category C: Severely Symptomatic

  10. Immunologic Parameters in Children • Absolute CD4+ counts in healthy children are much higher than in adults • Normal absolute CD4+ counts slowly decline to adult levels by age 6 • If using CD4+ count for ARV decision, use appropriate levels • CD4 percent varies less with age and may be a better immunologic parameter to follow in children <6 years

  11. Immunologic Parameters in Children • Obtain baseline CD4 assays when child is clinically stable • Confirm CD4 changes with a second test before making therapy decisions (when to initiate therapy, when to change therapy, etc.)

  12. HIV RNA and Children:Clinical Considerations • HIV RNA and CD4 assays are independently predictive of risk of disease progression • Both help determine when to start and when to change ARV therapy • A 5-fold change in HIV RNA copies/mL in infants or 3-fold change in children is biologically and clinically significant

  13. HIV RNA and Children:Clinical Considerations • Low levels at birth rise to >100,000 copies/mL to several million copies within the first 1–2 months of life • Without treatment, very slow decline over several years to reach “set point”

  14. HIV RNA and Children:Clinical Considerations • Children >12 months with HIV RNA >100,000 copies/mL are at higher risk for disease progression and death • Predictive value of HIV RNA in infants <12 months old less than older children • In infants, HIV RNA levels are much higher and overlap with rapid and non-rapid progressors • CD4+ counts/percentages may be more useful in evaluating risk in infants <12 months than HIV RNA; in older children both parameters are useful

  15. HIV RNA in Children:Clinical Considerations • Moderate predictive value of specific HIV RNA levels for disease progression/death in individual child • HIV RNA levels difficult to interpret in first year of life • CD4+ and HIV RNA level provide complimentary and independent information about prognosis • Assess HIV RNA every 3-4 months

  16. HIV RNA and Children:Clinical Considerations • Obtain 2 baseline HIV RNA tests when child is clinically stable • Confirm HIV RNA changes with a second test before making therapy changes • Consult pediatric HIV specialist when interpreting HIV RNA for clinical decision-making

  17. Antiretroviral Treatment Guidelines for Children with HIV Infection

  18. Decision Factors about ARV Initiation in Children • Disease severity and risk of progression—presence/hx of serious illness, CD4+ count, HIV RNA • Availability of appropriately formulated and palatable drugs

  19. Decision Factors about ARV Initiation in Children • Complexity of regimen and potential adverse effects • Effect of initial choice on later therapeutic options

  20. Decision Factors about ARV Initiation in Children • Presence of comorbidities (e.g. TB, Hep B or C, or chronic renal/liver disease) • Potential ARV interaction with child’s other medications • Ability of the child and caregiver to adhere to the regimen

  21. Early Initiation of Therapy: Potential Advantages Starting ARVs in the asymptomatic patient: • Controls viral replication while genetic quasispecies are relatively homogeneous and before significant viral mutations occur • Could control development of heterogeneous viral strains/mutations • Potentially leads to less drug resistance • Could lower “viral setpoint”fewer viral strains • Slows immune system destruction preserving immune function and preventing clinical progression

  22. Delayed Initiation of Therapy: Potential Advantages Delaying ARV therapy until symptomatic: • Could reduce evolution of drug-resistant virus due to lack of drug selection pressure exerted by early ARV use • May support greater adherence when symptomatic • Reduces or delays adverse effects of ARVs

  23. ARV Therapy for Infants <12 Months • Risk of disease progression is inversely correlated with age • Limited data on rapid v. slower disease • Limited clinical trial data on early aggressive therapy • Limited information on drug dosing • Potential ARV toxicities over the long term

  24. ARV Therapy for Infants <12 Months • Initiate treatment for any infant with clinical or immunologic symptoms • Consider treatment for infants who are asymptomatic with normal immune function The Working Group recommends:

  25. Indications for Initiation of ARV Therapy in Children <12 Months of Age

  26. ARV Therapy for Children Age 12 Months and Older • Risk of disease progression is less in older children than in infants • Children with fewer clinical symptoms or only moderate immune suppression are at lower risk for progression than those with more advanced clinical symptoms/immune disease • In children >12 months, plasma HIV RNA may provide information about progression risk as an adjunct to clinical/immune parameters and can assist in making ARV decisions

  27. ARV Therapy for Children Age 12 Months and Older • Start treatment in children with AIDS or severe immune suppression • Consider treatment for children with • Mild-moderate clinical symptoms • Moderate immune suppression and/or • Confirmed plasma HIV RNA level >100,000 copies/mL The Working Group recommends:

  28. ARV Therapy for Children Age 12 Months and Older • Defer treatment in asymptomatic children with normal immune status with low risk of clinical disease (HIV RNA <100,000 copies/mL) when adherence factors favor postponing • Monitor virologic, clinical, and immunologic status

  29. ARV Therapy for Children Age 12 Months and Older • Factors to consider in deciding when to initiate therapy • Increasing HIV RNA levels (>100,000 copies/mL) • Rapidly declining CD4+ count or percentage to values approaching severe suppression • Development of clinical symptoms • Ability of caregiver and child to adhere to regimen